Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitation(s) is/are: means of fluorescence microscopy techniques in claim 1, last two lines.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
Examiner notes that fluorescence microscopy techniques is interpreted to encompass fluorescence microscopy techniques disclosed by Applicant such as in paragraphs 0036 and 0081, and their equivalents.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventors, at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
The claims require:
an Fab fragment or antibody that binds to GPCR (in claim 1, line 6);
an Fab fragment or antibody that binds G-protein or arrestin (in claim 1, line 11);
a rabbit polyclonal antibody of the IgG2b type (in claim 5, line 3);
a mouse monoclonal antibody of the IgG1 type (in claim 5, line 4);
Fab fragment derived from an antibody that is a rabbit polyclonal antibody of the IgG2b type (claim 5, line 5);
a mouse monoclonal antibody of the IgG1 type (claim 5, line 6);
fluorescent donor probe that comprises an anti-CXCR1 and anti-CXCR2 Fab fragment or antibody (claim 6, lines 2-3);
fluorescent acceptor probe that comprises an anti-sub unit G-α-1 and/or anti-β-arrestin 1 and/or anti-β-arrestin 2 Fab fragment or antibody (claim 7, lines 3-4);
clone #501 (claim 8, line 5);
clone 3HCLC (claim 8, line 5);
clone 42705,111 (claim 8, line 5);
clone PA5-87555 (claim 8, line 5);
clone PA5-35089 (claim 8, line 5);
antiserum PA1-1000 (claim 8, line 6); and
a pharmacological modulator of interleukin-8 receptors (claim 10, line 4).
The specification does not describe which amino acid residues, nucleic acid residues or other molecular components are responsible for the functions claimed [i.e., the binding function recited]. Potential agents must first be screened in an assay to ascertain if the agents have the functions required by the instant claims. A few examples of potential generic agents does not disclose the structures common to all members of the genus of encompassed by the broad claimed limitations. The specification does not disclose the structure of all of the claimed variant agents and fails to disclose which regions of the agents are responsible for the functions claimed. In the absence of a known or disclosed correlation between structure and function, claims which encompass variants defined by their function are generally not considered described.
Applicant is directed to MPEP § 2163 for guidelines on compliance with the written description requirement. Here, applicant has not described a reasonable number of members of the genus of agents that bind to the claimed limitation, i.e. the required starting materials for the claims, but rather has presented the public with an idea of how to perform an assay that might identify some peptides that fall within the scope of the claim. Of course, depending on what agents are used in the screening assay, it may well identify none. The Court of Appeals for the Federal Circuit addressed claims of this sort in great detail in University of Rochester v. G.D. Searle and Co. (69 USPQ 2nd 1886, CAFC 2004). In Rochester, the Federal Circuit upheld the district court's ruling that patent claims which recited administration of compounds not disclosed, but rather to be identified in a screening assay, were invalid on their face.
Regarding the scope of the claims that includes antibodies that bind to the recited limitation, the specification does not describe the structure of the full genus of antibodies responsible for each of the functions claimed. The Federal Circuit has clarified Written Description as it applies to antibodies in the recent decision Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017). The Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. 112(a) (or pre-AIA first paragraph) requires adequate written description of the antibody itself. Amgen, 872 F.3d at 1378-79. The Amgen court expressly stated that the so-called “newly characterized antigen” test, which had been based on an example in USPTO-issued training materials and was noted in dicta in several earlier Federal Circuit decisions, should not be used in determining whether there is adequate written description under 35 U.S.C. 112(a) for a claim drawn to an antibody. Citing its decision in Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., the court also stressed that the “newly characterized antigen” test could not stand because it contradicted the quid pro quo of the patent system whereby one must describe an invention in order to obtain a patent. Amgen, 872 F.3d at 1378-79, quoting Ariad, 598 F.3d 1336, 1345 (Fed. Cir. 2010). In view of the Amgen decision, adequate written description of an antigen alone is not considered adequate written description of a claimed antibody to that antigen, even when preparation of such an antibody is routine and conventional. Id.
While generically the structure of antibodies is known, the structure of the presently recited antibodies can vary substantially within the above given claimed recitations. As noted in Amgen, knowledge that an antibody binds to a particular epitope on an antigen tells one nothing at all about the structure of the antibody, wherein “instead of analogizing the antibody-antigen relationship to a ‘key in a lock,’ it [is] more apt to analogize it to a lock and ‘a ring with a million keys on it.” (Internal citations omitted). The relevant antibody art confirms this quandary, indicating that “knowledge of an epitope or antigen used to generate a monoclonal antibody is insufficient for making the original antibody available, even if suitable in vitro test systems for screening are used.” See p. 8, lines 3-5 of WO 2009/033743 A1. Therefore, those of skill in the art would not accept that the inventor had been in possession of the full genus of antibodies presently claimed.
Functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Abbvie Deutschland GMBH & Co. v. Janssen Biotech, Inc. (759 F.3d 1285 (Fed. Cir. 2014). “When a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus." Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005).
Consequently, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus of binding agents (including antibodies) nor guidance as to which of the myriad of molecules encompassed by the binding agents would meet the limitations of the claims. Further, given the well-known high level of polymorphism of immunoglobulins and antibodies, the skilled artisan would not have recognized that applicant was in possession of the vast repertoire of antibodies encompassed by the claimed invention.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111 (Fed. Cir. 1991), clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
The skilled artisan cannot envision the detailed chemical structure of the genus of binding agents, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of identification. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016 (Fed. Cir. 1991). Therefore, the instant claims do not meet the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Lohse et al., “Kinetic Analysis of G protein-coupled receptor signaling using fluorescence resonance energy transfer in living cells” Advances in Protein Chemistry, Academic Press, New York, NY, US Pages 167-188, 1 January 2007. (Cited in Applicant’s IDS). This reference teaches FRET for analyzing interaction between a GPCR and its G protein heterotrimer (and arrestin). The interaction partners are labeled with genetically encoded acceptors/donors. See fig. 2c, p. 175 discussing “FIG 2”, 176 in para. 1, p. 182 discussing “Receptor-G protein Interaction”. (However, this reference does not disclose or teach that the FRET donor and acceptors are labeled by antibodies.)
Craig et al., “Fluorescent ligands, antibodies, and proteins for the study of receptors”, Pharmacology & Therapeutics, vol. 100, no. 2, 1 November 2003, pages 101-118. (Cited in Applicant’s IDS). This reference teaches GPCR, fluorescence-based methods have enabled visualization of agonist-stimulated receptor clustering, degradation of the receptor-ligand complex…, and visualization of formation of receptor complexes. The reference discloses labeling of receptors, relying on GFP, antibodies and fluorescent ligands for the purpose of studying GPCR. Receptor and G-protein or arrestin interaction are discussed. See abstract and throughout article. The technique of fluorescence resonance energy transfer [FRET] in general and its history is also disclosed. See pp. 110-112, under section 3.5. (However, this reference does not teach or suggest a fluorophore group, of a fluorescent donor probe, linked via amide bond to amino group of a N-terminal amino acid of an anti-GPCR Fab fragment or antibody, and a fluorescent group, of a fluorophore acceptor probe, linked via amide bond to an amino group of an anti-G-protein and/or anti-arrestin Fab fragment or antibody, and their interaction that can be visualized via the FRET system.)
Snapp et al., “Rational Design and Evaluation of FRET Experiments to Measure Protein Proximities in Cells”, Curr Protoc Cell Biol. 2006 October; Chapter: Unit –17.9. (Cited in Applicant’s IDS.) This reference teaches use of FRET to report on close (subnanometer) proximities of fluorescently marked proteins. Measurement of FRET between two appropriately labeled proteins containing fluorophores with suitable properties can be used to infer the spatial and temporal characteristics of protein interactions in their native cellular environment. See abstract. (However, this reference does not discuss or suggest the possibility of evaluation of GPCR interaction with G-proteins or arrestin using FRET, nor specifically using FRET donor and acceptor labeled by antibodies. In particular, this reference does not teach or suggest a fluorophore group, of a fluorescent donor probe, linked via amide bond to amino group of a N-terminal amino acid of an anti-GPCR Fab fragment or antibody, and a fluorescent group, of a fluorophore acceptor probe, linked via amide bond to an amino group of an anti-G-protein and/or anti-arrestin Fab fragment or antibody, and their interaction that can be visualized via the FRET system.)
CA 3127858 (“Roux”). This reference teaches antibody labeled with fluorescent lable for TR-FRET. See abstract. (However, this reference does not discuss or suggest the possibility of evaluation of GPCR interaction with G-proteins or arrestin using FRET, nor specifically using FRET donor and acceptor labeled by antibodies.)
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Ann Montgomery whose telephone number is (571)272-0894. The examiner can normally be reached Mon-Fri, 9-5:30 PM PST.
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/Ann Montgomery/Primary Examiner, Art Unit 1678
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